Data is available on Synapse.

Summary

This includes code and plots for the final version of the paper. Exploratory analysis and intermediate processing steps are too extensive to be included here

Sendai Expression

Biotype of expressed genes

Biotype Count
protein_coding 11681
processed_transcript 1691
antisense 1488
lincRNA 879
processed_pseudogene 822
nonsense_mediated_decay 708
retained_intron 671
sense_intronic 197
unprocessed_pseudogene 163
sense_overlapping 93
miRNA 66
misc_RNA 58
snoRNA 56
transcribed_unprocessed_pseudogene 47
pseudogene 37
transcribed_processed_pseudogene 28
snRNA 27
unitary_pseudogene 16
3prime_overlapping_ncrna 12
rRNA 8
Mt_tRNA 4
polymorphic_pseudogene 4
non_stop_decay 3
IG_V_pseudogene 1
TR_C_gene 1

Check sex on 94 samples

genes_on_chrY
USP9Y
UTY
NLGN4Y
ZFY
RPS4Y1
TXLNG2P

Detect sample contamination with VerifyBamID

The labeling of Donor 499 was corrected manually

Excluded due to sample mislabeling, contamination or issues with expression on the sex chromosomes

Sample.Name
1275-B-3F
1275-B-3N
1275-C-1F
1275-C-1N
2476-1-4F
2476-1-4N
2484-2aF
2484-2aN
3113-3-21F
3113-3-21N
3121-2-1F
3121-2-1N
3121-2-MSSM2F
3121-2-MSSM2N
3130-2-1F
3130-2-1N
676-1-2N

Samples included in analysis

6_wk_FB_neuron NPC
CT 20 20
SZ 19 18
Case Control
10 9

QC metrics

Check sex on cleaned dataset

Differential gene expression based on Sendai virus exression

[1] “DE genes at FDR < 5%: 2738”

Yaminaka factors

POU5F1 is not expressed at a sufficient level

logFC AveExpr t P.Value qvalue gene
ENSG00000136997 0.3021708 3.1929949 2.1221004 0.0371472 0.0865717 MYC
ENSG00000181449 -0.0561620 8.7614381 -1.0330145 0.3049324 0.2868959 SOX2
ENSG00000136826 -0.1388002 0.0752657 -0.8533798 0.3961789 0.3310979 KLF4

Compare Neurons and NPC

Enrichments for genes up in Neurons

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
tissue_exp_brain 495.00 65.97 241 3.65 9.20E-84
c2.BENPORATH_ES_WITH_H3K27ME3 730.00 97.29 283 2.91 2.29E-70
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347.00 46.25 162 3.50 7.81E-53
c2.BENPORATH_SUZ12_TARGETS 664.00 88.50 240 2.71 9.40E-53
c2.BENPORATH_EED_TARGETS 705.00 93.96 240 2.55 2.13E-47
c2.BENPORATH_PRC2_TARGETS 391.00 52.11 163 3.13 5.01E-45
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225.00 163.27 340 2.08 1.26E-44
c2.MIKKELSEN_MCV6_HCP_WITH_H3K27ME3 285.00 37.98 129 3.40 2.42E-40
c2.MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3 215.00 28.65 108 3.77 3.83E-39
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMBRANE 998.00 133.01 282 2.12 3.13E-38
c5.GO_CELL_CELL_SIGNALING 502.00 66.91 173 2.59 7.35E-35
c5.GO_NEURON_PART 1088.00 145.01 282 1.94 5.04E-31
c2.MIKKELSEN_NPC_HCP_WITH_H3K27ME3 192.00 25.59 90 3.52 7.31E-30
c2.NABA_MATRISOME 555.00 73.97 174 2.35 2.58E-29
c5.GO_SYNAPSE 677.00 90.23 198 2.19 7.62E-29
c5.GO_SYNAPTIC_SIGNALING 331.00 44.11 123 2.79 1.94E-28
c2.ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY 873.00 116.35 235 2.02 2.55E-28
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223.00 29.72 96 3.23 3.72E-28
tissue_exp_testis 452.00 60.24 149 2.47 9.65E-28
c5.GO_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY 298.00 39.72 112 2.82 1.80E-26

Enrichments for genes up in NPCs

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP 547 33.21 260 7.83 4.96E-176
c2.DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP 304 18.46 190 10.29 1.04E-156
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 41.89 247 5.90 7.73E-131
c2.KOBAYASHI_EGFR_SIGNALING_24HR_DN 236 14.33 153 10.68 6.86E-129
c4.MODULE_54 241 14.63 150 10.25 2.58E-122
c2.ROSTY_CERVICAL_CANCER_PROLIFERATION_CLUSTER 137 8.32 111 13.34 2.69E-111
c7.GSE15750_DAY6_VS_DAY10_TRAF6KO_EFF_CD8_TCELL_UP 186 11.29 122 10.80 3.20E-103
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_UP 1176 71.40 282 3.95 6.11E-101
c2.SHEDDEN_LUNG_CANCER_POOR_SURVIVAL_A6 416 25.26 170 6.73 6.49E-99
c7.GSE15750_DAY6_VS_DAY10_EFF_CD8_TCELL_UP 189 11.48 119 10.37 1.86E-97
c5.GO_CHROMOSOME 778 47.24 226 4.78 2.87E-97
c2.CHANG_CYCLING_GENES 145 8.80 103 11.70 1.19E-92
c5.GO_CHROMOSOME_ORGANIZATION 875 53.13 233 4.39 8.60E-92
c2.SOTIRIOU_BREAST_CANCER_GRADE_1_VS_3_UP 147 8.93 102 11.43 4.80E-90
c2.ZHANG_TLX_TARGETS_60HR_DN 263 15.97 131 8.20 3.32E-89
c2.REACTOME_CELL_CYCLE 384 23.31 155 6.65 6.43E-89
h.HALLMARK_E2F_TARGETS 199 12.08 115 9.52 5.45E-88
c2.PUJANA_BRCA2_PCC_NETWORK 388 23.56 153 6.49 5.80E-86
c7.GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_12H_UP 171 10.38 105 10.11 3.42E-84
c2.WHITEFORD_PEDIATRIC_CANCER_MARKERS 110 6.68 86 12.88 1.49E-83

Overlap between NPC and neuron

## 
## Attaching package: 'sets'
## The following object is masked from 'package:igraph':
## 
##     %>%
## The following object is masked from 'package:synapseClient':
## 
##     set
## [1] "cutoff: log2 RPKM > 0"

## [1] "cutoff: log2 RPKM > 1"

## [1] "cutoff: log2 RPKM > 2"

## [1] "cutoff: log2 RPKM > 3"

## [1] "cutoff: log2 RPKM > 4"

## [1] "cutoff: log2 RPKM > 5"

## [1] "cutoff: log2 RPKM > 6"

Cibersort results

Histogram of cell type composition: all samples

There is no case-control difference in cell type scores

Cell composition in Neurons and NPC

Differential expression based on cell fraction

Enrichment test for gene positively correlated with cell fraction

6_wk_FB_neuron-Astrocytes
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
CMC-modules_peru 114 67 108 1.6 2.5e-18
CMC-modules_lightgreen 199 118 173 1.5 6.0e-18
c4.MODULE_1 318 188 253 1.3 4.5e-15
c2.LEE_BMP2_TARGETS_UP 598 354 442 1.2 1.0e-14
c2.MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H 826 488 584 1.2 9.7e-13
c4.MODULE_47 196 116 162 1.4 1.0e-12
c5.GO_EXTRACELLULAR_STRUCTURE_ORGANIZATI 220 130 179 1.4 1.1e-12
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSI 177 105 148 1.4 1.5e-12
c4.MODULE_2 328 194 252 1.3 7.0e-12
c2.BOQUEST_STEM_CELL_UP 207 122 168 1.4 8.3e-12
6_wk_FB_neuron-Neuron
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 340 438 1.3 5.2e-26
CMC-modules_red 689 473 566 1.2 1.6e-16
CMC-modules_blue 1154 792 904 1.1 1.7e-14
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 238 294 1.2 2.7e-12
c5.GO_SYNAPTIC_SIGNALING 331 227 278 1.2 8.4e-11
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 113 146 1.3 1.6e-09
c5.GO_CELL_CELL_SIGNALING 502 344 403 1.2 1.8e-09
secondary_FMRP-targets 770 528 600 1.1 2.7e-09
abnormal_synaptic_transmission 386 265 315 1.2 4.0e-09
c5.GO_SYNAPSE 677 465 531 1.1 4.2e-09
6_wk_FB_neuron-Oligodendrocyte_Precursor_Cell
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 779 920 1.2 2.8e-19
CMC-modules_peru 114 73 108 1.5 3.5e-15
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 348 430 1.2 9.0e-15
c2.MILI_PSEUDOPODIA_HAPTOTAXIS_DN 626 398 483 1.2 7.6e-14
c5.GO_PROTEIN_COMPLEX_SUBUNIT_ORGANIZATI 1299 826 947 1.1 8.1e-14
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223 142 189 1.3 1.6e-12
c2.LU_AGING_BRAIN_UP 239 152 199 1.3 1.3e-11
c5.GO_ENDOPLASMIC_RETICULUM 1285 818 924 1.1 3.4e-11
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 253 312 1.2 4.8e-11
c5.GO_ENDOPLASMIC_RETICULUM_PART 926 589 679 1.2 6.4e-11
6_wk_FB_neuron-Fibroblast
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.REN_ALVEOLAR_RHABDOMYOSARCOMA_DN 391 278 352 1.3 3.1e-20
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 871 992 1.1 9.7e-17
CMC-modules_lightcyan 268 191 243 1.3 2.8e-15
c2.BLALOCK_ALZHEIMERS_DISEASE_UP 1486 1056 1180 1.1 1.1e-14
c5.GO_ENDOPLASMIC_RETICULUM 1285 913 1027 1.1 3.2e-14
c5.GO_ENDOPLASMIC_RETICULUM_PART 926 658 752 1.1 2.1e-13
c4.MODULE_1 318 226 278 1.2 2.0e-12
c4.MODULE_47 196 139 178 1.3 1.1e-11
c5.GO_MOVEMENT_OF_CELL_OR_SUBCELLULAR_CO 951 676 764 1.1 1.1e-11
c5.GO_LOCOMOTION 785 558 634 1.1 1.2e-10
6_wk_FB_neuron-MEF
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c5.GO_POLY_A_RNA_BINDING 1113 805 970 1.2 4.9e-35
c5.GO_RNA_BINDING 1466 1060 1239 1.2 3.8e-31
c5.GO_RIBONUCLEOPROTEIN_COMPLEX 660 477 595 1.2 9.9e-31
c4.MODULE_83 308 223 297 1.3 2.3e-29
pli_MID 2881 2083 2308 1.1 9.3e-27
c2.HSIAO_HOUSEKEEPING_GENES 374 270 350 1.3 3.6e-26
c4.MODULE_114 319 231 301 1.3 2.1e-24
c5.GO_RIBONUCLEOPROTEIN_COMPLEX_BIOGENES 419 303 384 1.3 1.4e-23
c4.MODULE_151 298 215 281 1.3 1.0e-22
c5.GO_RNA_PROCESSING 781 565 674 1.2 7.1e-22
6_wk_FB_neuron-Myocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c5.GO_RNA_BINDING 1466 994 1240 1.2 6.7e-53
c5.GO_POLY_A_RNA_BINDING 1113 755 963 1.3 4.7e-50
c2.PUJANA_BRCA1_PCC_NETWORK 1476 1001 1214 1.2 3.9e-39
c5.GO_RIBONUCLEOPROTEIN_COMPLEX 660 448 587 1.3 2.2e-38
CMC-modules_brown 897 608 766 1.3 2.7e-35
c4.MODULE_83 308 209 295 1.4 7.7e-35
c5.GO_RNA_PROCESSING 781 530 674 1.3 4.0e-34
c4.MORF_UBE2I 236 160 231 1.4 1.2e-32
c4.MODULE_114 319 216 302 1.4 1.4e-32
c4.MORF_CSNK2B 286 194 274 1.4 1.7e-32
6_wk_FB_neuron-hiPSC
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 347 507 1.5 5.6e-37
c2.MANALO_HYPOXIA_DN 279 140 240 1.7 8.6e-37
c5.GO_CHROMOSOME_ORGANIZATION 875 440 613 1.4 2.8e-34
c2.PUJANA_CHEK2_PCC_NETWORK 730 367 522 1.4 7.6e-33
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 275 404 1.5 2.3e-30
c2.PUJANA_BRCA1_PCC_NETWORK 1476 743 949 1.3 4.3e-30
c5.GO_CHROMOSOME 778 391 543 1.4 1.0e-29
c2.DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP 304 153 244 1.6 9.5e-28
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 616 797 1.3 1.1e-27
c2.LEE_BMP2_TARGETS_DN 826 416 564 1.4 5.3e-27
NPC-Astrocytes
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 320 401 1.3 4.0e-16
secondary_FMRP-targets 770 498 597 1.2 1.6e-15
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMB 998 645 730 1.1 2.2e-09
c5.GO_NEURON_PART 1088 704 790 1.1 4.5e-09
c5.GO_REGULATION_OF_NEUROTRANSMITTER_LEV 165 107 140 1.3 5.2e-09
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 1000 647 728 1.1 9.2e-09
c5.GO_SYNAPTIC_SIGNALING 331 214 261 1.2 1.0e-08
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 792 881 1.1 1.2e-08
c2.BENPORATH_ES_WITH_H3K27ME3 730 472 541 1.1 1.4e-08
c4.MODULE_66 474 307 361 1.2 3.0e-08
NPC-Neuron
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 279 399 1.4 5.7e-31
c2.BENPORATH_ES_WITH_H3K27ME3 730 411 507 1.2 7.0e-14
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 224 294 1.3 1.0e-13
secondary_FMRP-targets 770 434 528 1.2 7.1e-13
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 93 136 1.5 8.6e-13
c2.BENPORATH_SUZ12_TARGETS 664 374 455 1.2 3.5e-11
CMC-modules_blue 1154 650 754 1.2 6.4e-11
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 196 253 1.3 8.5e-11
CMC-modules_red 689 388 468 1.2 1.3e-10
c5.GO_NEURON_PART 1088 613 711 1.2 2.2e-10
NPC-Oligodendrocyte_Precursor_Cell
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
secondary_FMRP-targets 770 498 586 1.2 1.5e-12
c5.GO_CELL_PROJECTION 1508 975 1088 1.1 4.7e-11
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 1000 647 733 1.1 1.0e-09
c5.GO_NEURON_PROJECTION 835 540 614 1.1 1.1e-08
c5.GO_VACUOLE 959 620 699 1.1 1.3e-08
c5.GO_GOLGI_APPARATUS 1210 782 864 1.1 1.3e-07
c5.GO_NEURON_PART 1088 703 781 1.1 1.4e-07
c2.BERENJENO_TRANSFORMED_BY_RHOA_DN 365 236 281 1.2 1.8e-07
primary_PSD_(human_core) 644 416 476 1.1 1.8e-07
c5.GO_VACUOLAR_PART 577 373 429 1.1 2.4e-07
NPC-Newly_Formed_Oligodendrocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 285 415 1.5 2.9e-37
c2.BENPORATH_ES_WITH_H3K27ME3 730 420 557 1.3 1.3e-27
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 200 283 1.4 5.6e-22
c2.BENPORATH_SUZ12_TARGETS 664 382 494 1.3 1.7e-20
c2.MIKKELSEN_MCV6_HCP_WITH_H3K27ME3 285 164 235 1.4 1.2e-19
c2.BENPORATH_PRC2_TARGETS 391 225 306 1.4 2.0e-18
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 228 308 1.3 1.5e-17
tissue_exp_testis 452 260 342 1.3 2.3e-16
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 704 837 1.2 3.7e-16
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMB 998 574 687 1.2 1.9e-14
NPC-Fibroblast
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.NABA_MATRISOME 555 306 397 1.3 6.3e-16
c2.WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216 297 164 230 1.4 6.6e-16
Peptide_chain_elongation 82 45 77 1.7 6.3e-15
c2.REACTOME_PEPTIDE_CHAIN_ELONGATION 84 46 78 1.7 2.3e-14
Eukaryotic_Translation_Elongation 84 46 78 1.7 2.3e-14
Formation_of_a_pool_of_free_40S_subunit 92 51 84 1.7 3.1e-14
Viral_mRNA_Translation 83 46 77 1.7 4.0e-14
viral transcription 82 45 76 1.7 6.7e-14
c2.LEE_BMP2_TARGETS_UP 598 330 417 1.3 8.4e-14
3’_-UTR-mediated_translational_regulati 102 56 90 1.6 5.4e-13
NPC-MEF
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c4.MORF_RAD23A 343 240 319 1.3 1.3e-26
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 482 598 1.2 2.8e-26
c4.MORF_BUB3 275 192 261 1.4 6.6e-26
c2.PUJANA_BRCA1_PCC_NETWORK 1476 1031 1194 1.2 3.3e-24
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 821 966 1.2 1.0e-23
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 382 479 1.3 2.2e-23
c4.MORF_CSNK2B 286 200 266 1.3 2.2e-22
c2.DIAZ_CHRONIC_MEYLOGENOUS_LEUKEMIA_UP 1312 916 1059 1.2 7.7e-21
c2.SOTIRIOU_BREAST_CANCER_GRADE_1_VS_3_U 147 103 145 1.4 1.9e-20
c5.GO_CELL_CYCLE 1180 824 957 1.2 4.6e-20
NPC-Myocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.PUJANA_BRCA1_PCC_NETWORK 1476 754 1005 1.3 3.9e-44
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 625 854 1.4 1.2e-43
c2.PUJANA_CHEK2_PCC_NETWORK 730 373 546 1.5 2.9e-41
CMC-modules_black 625 319 474 1.5 1.6e-38
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 600 810 1.3 4.7e-38
c2.CAIRO_HEPATOBLASTOMA_CLASSES_UP 581 297 434 1.5 1.2e-32
c2.JOHNSTONE_PARVB_TARGETS_3_DN 862 440 598 1.4 2.5e-29
c2.RODRIGUES_THYROID_CARCINOMA_POORLY_DI 604 308 440 1.4 6.5e-29
c2.LEE_BMP2_TARGETS_DN 826 422 575 1.4 7.9e-29
c4.GNF2_EIF3S6 118 60 114 1.9 1.6e-28
NPC-hiPSC
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.PUJANA_BRCA1_PCC_NETWORK 1476 852 1123 1.3 3.6e-54
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 679 913 1.3 2.7e-50
c2.PUJANA_CHEK2_PCC_NETWORK 730 421 593 1.4 1.8e-43
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 316 460 1.5 1.9e-41
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 398 559 1.4 2.6e-40
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 706 914 1.3 5.5e-38
c2.PUJANA_BRCA2_PCC_NETWORK 388 224 337 1.5 1.5e-36
c2.CAIRO_HEPATOBLASTOMA_CLASSES_UP 581 335 473 1.4 3.4e-35
Cell_Cycle 455 263 382 1.5 3.4e-34
h.HALLMARK_E2F_TARGETS 199 115 188 1.6 1.9e-32

Analysis of original data

Analysis after correcting for cell type composition scores for fibroblasts and MEF

Color PCA by CTC score

Fit linear model to test difference in CTC scores between cell types

Correlation of CTC scores with principal components

## Projected run time: ~ 20 min
## Projected run time: ~ 1 min
## [1] 0.02234939
## [1] 0.02350184
## [1] 0.003482901
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  vpCellFrac2$Donor and vpCellFrac_minimal$Donor
## V = 39876000, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0

all cell fractions

accounting for MEF and Fibroblast increases donor contributions

## Projected run time: ~ 1 min
## Projected run time: ~ 1 min
## 
##  Paired t-test
## 
## data:  df$adjusted and df$original
## t = 15.712, df = 18909, p-value < 2.2e-16
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  0.003048411 0.003917390
## sample estimates:
## mean of the differences 
##             0.003482901

Percent bars

VariancePartition within each cell type

Compare donor effect

variancePartition: include technical variables

## Projected run time: ~ 5 min

Correlation between covariates

Differential expression between cases and controls in combined NPC + neuron dataset

Volcano plot

Genes with FDR < 30%

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -3.8867431 -2.0458924 -7.503823 0.0000000 0.0000020 ENSG00000230847
ENSG00000164930 -0.7773348 4.8643554 -5.911893 0.0000001 0.0008782 FZD6
ENSG00000226259 -1.1458273 2.3980778 -5.496058 0.0000005 0.0031800 GTF2H2B
ENSG00000236725 -1.0340737 0.4658067 -5.316601 0.0000011 0.0039572 ENSG00000236725
ENSG00000269337 -1.0984407 0.7260166 -5.313372 0.0000011 0.0039572 ENSG00000269337
ENSG00000169629 -0.9328454 2.8967989 -4.990793 0.0000039 0.0116728 RGPD8
ENSG00000184988 -0.6371885 0.6108187 -4.752049 0.0000097 0.0199287 TMEM106A
ENSG00000177873 -0.4751565 3.6251045 -4.744838 0.0000100 0.0199287 ZNF619
ENSG00000145246 0.8099405 3.4869808 4.737294 0.0000103 0.0199287 ATP10D
ENSG00000121691 1.5711365 4.3941262 4.717053 0.0000111 0.0199287 CAT
ENSG00000003402 -1.2184673 2.9784138 -4.658510 0.0000138 0.0225783 CFLAR
ENSG00000173894 0.3974699 5.3493957 4.539741 0.0000215 0.0322191 CBX2
ENSG00000237945 -1.4449894 3.0295611 -4.474223 0.0000273 0.0378749 LINC00649
ENSG00000037757 -1.0264047 3.0641913 -4.421709 0.0000332 0.0403826 MRI1
ENSG00000115828 -1.4442631 0.6431161 -4.417693 0.0000336 0.0403826 QPCT
ENSG00000181234 3.9832515 -0.9565400 4.375613 0.0000392 0.0441347 TMEM132C
ENSG00000164669 -0.9330823 -0.2461149 -4.356789 0.0000420 0.0444782 INTS4L1
ENSG00000240342 -0.6669021 4.8380931 -4.336412 0.0000452 0.0452268 RPS2P5
ENSG00000229404 -1.7586482 -0.9581430 -4.311301 0.0000495 0.0466317 LINC00858
ENSG00000254353 -2.1384802 -0.4100724 -4.291721 0.0000531 0.0466317 ENSG00000254353
ENSG00000226002 0.5981007 0.1750937 4.285220 0.0000544 0.0466317 ENSG00000226002
ENSG00000244026 -0.5236215 3.8687373 -4.177683 0.0000799 0.0653742 FAM86DP
ENSG00000185985 2.7724325 5.1279631 4.162363 0.0000843 0.0660238 SLITRK2
ENSG00000236383 -0.6271087 -0.4722674 -4.146970 0.0000891 0.0668164 LINC00854
ENSG00000229789 -1.2992945 -0.2195011 -4.131695 0.0000940 0.0677005 ENSG00000229789
ENSG00000010704 -0.9534242 -0.6692788 -4.104042 0.0001036 0.0709274 HFE
ENSG00000228463 -1.3430626 -0.4915192 -4.096619 0.0001064 0.0709274 ENSG00000228463
ENSG00000115507 1.9964444 -0.0009156 4.075118 0.0001147 0.0725178 OTX1
ENSG00000239959 -0.7577011 -0.1855192 -4.069923 0.0001168 0.0725178 ENPP7P2
ENSG00000162618 -1.6783969 -0.7365519 -4.043841 0.0001279 0.0733200 ELTD1
ENSG00000198715 -0.6225848 2.0519971 -4.037013 0.0001310 0.0733200 C1orf85
ENSG00000107829 -0.5636433 1.8306642 -4.028719 0.0001349 0.0733200 FBXW4
ENSG00000196569 -1.2655757 3.3493015 -4.027240 0.0001356 0.0733200 LAMA2
ENSG00000221870 2.5063090 1.4534521 4.021192 0.0001385 0.0733200 TMEM257
ENSG00000227775 0.4286190 4.0581385 3.993127 0.0001526 0.0785141 ENSG00000227775
ENSG00000160789 -0.3087472 6.1850559 -3.945999 0.0001796 0.0886165 LMNA
ENSG00000212719 -2.8235614 2.0022500 -3.938600 0.0001842 0.0886165 C17orf51
ENSG00000259085 0.4518444 0.8237710 3.934224 0.0001870 0.0886165 ENSG00000259085
ENSG00000137962 -0.8405123 5.9505584 -3.925476 0.0001927 0.0889780 ARHGAP29
ENSG00000148942 -1.7992311 -0.7765750 -3.905677 0.0002063 0.0928457 SLC5A12
ENSG00000234431 -1.1610396 -0.0453674 -3.836649 0.0002609 0.1145893 ENSG00000234431
ENSG00000106868 -0.4221252 5.3831940 -3.801357 0.0002940 0.1260332 SUSD1
ENSG00000256043 -1.1396397 2.1885944 -3.734748 0.0003676 0.1484549 CTSO
ENSG00000183036 1.0568761 0.2824591 3.731252 0.0003719 0.1484549 PCP4
ENSG00000255983 -1.7770246 -1.6255799 -3.724899 0.0003799 0.1484549 ENSG00000255983
ENSG00000108946 -0.1539076 8.5710566 -3.720296 0.0003857 0.1484549 PRKAR1A
ENSG00000118946 -0.6964719 6.9945080 -3.710494 0.0003985 0.1484549 PCDH17
ENSG00000146833 -1.7925956 2.0933749 -3.708006 0.0004018 0.1484549 TRIM4
ENSG00000238286 0.3957608 0.6291523 3.706382 0.0004040 0.1484549 SLC35E1P1
ENSG00000234719 -0.9946496 0.9947928 -3.679553 0.0004416 0.1590205 ENSG00000234719
ENSG00000222489 0.4179907 0.2003903 3.668398 0.0004582 0.1594946 ENSG00000222489
ENSG00000145736 -0.5293506 3.2139470 -3.666787 0.0004606 0.1594946 GTF2H2
ENSG00000234171 -0.3666779 2.5715243 -3.646265 0.0004929 0.1674384 ENSG00000234171
ENSG00000263535 -0.5471106 0.2504930 -3.637930 0.0005066 0.1676472 AK4P1
ENSG00000105963 -0.5320618 0.9723243 -3.629585 0.0005206 0.1676472 ADAP1
ENSG00000185518 -1.4407644 -0.7248376 -3.629134 0.0005214 0.1676472 SV2B
ENSG00000136104 0.3501590 3.8369805 3.609525 0.0005560 0.1715273 RNASEH2B
ENSG00000232300 0.5848956 -0.3102700 3.597250 0.0005788 0.1715273 FAM215B
ENSG00000266937 -0.2438614 1.6488055 -3.592392 0.0005880 0.1715273 ENSG00000266937
ENSG00000198932 -0.5232759 4.2805161 -3.590830 0.0005910 0.1715273 GPRASP1
ENSG00000105971 -0.4935931 4.8915284 -3.586868 0.0005987 0.1715273 CAV2
ENSG00000066382 1.6313657 3.2008651 3.586588 0.0005993 0.1715273 MPPED2
ENSG00000169436 2.9415822 -1.3911095 3.586128 0.0006002 0.1715273 COL22A1
ENSG00000022556 2.4000333 1.2777887 3.576075 0.0006201 0.1744663 NLRP2
ENSG00000227318 -1.7281778 -0.6086402 -3.568752 0.0006351 0.1751623 ENSG00000227318
ENSG00000170089 -0.4997211 2.3869475 -3.565386 0.0006421 0.1751623 ENSG00000170089
ENSG00000196993 -0.7658407 0.0667859 -3.556916 0.0006600 0.1773572 NPIPB9
ENSG00000217512 0.3593747 0.6649783 3.523761 0.0007347 0.1945323 ENSG00000217512
ENSG00000036448 0.7667332 1.7145378 3.512307 0.0007623 0.1953258 MYOM2
ENSG00000141837 -1.0014302 1.3880998 -3.507836 0.0007733 0.1953258 CACNA1A
ENSG00000269600 1.6893815 -1.3032529 3.507404 0.0007744 0.1953258 ENSG00000269600
ENSG00000169955 -0.6639366 1.6450844 -3.504748 0.0007811 0.1953258 ZNF747
ENSG00000176978 -0.4750891 3.9911880 -3.496565 0.0008019 0.1977826 DPP7
ENSG00000146707 -0.3052560 3.3309046 -3.484563 0.0008333 0.2027673 POMZP3
ENSG00000126822 0.9815936 4.3171322 3.470810 0.0008708 0.2090667 PLEKHG3
ENSG00000253954 0.8588332 -0.0100037 3.449438 0.0009323 0.2196709 HMGN1P38
ENSG00000011405 0.1496642 7.6232380 3.447050 0.0009394 0.2196709 PIK3C2A
ENSG00000105136 -0.1753927 4.7028745 -3.438130 0.0009665 0.2230963 ZNF419
ENSG00000128591 -0.9814583 5.8216396 -3.401220 0.0010863 0.2475970 FLNC
ENSG00000153406 0.5476832 1.1225174 3.392704 0.0011159 0.2511611 NMRAL1
ENSG00000259363 0.7834232 0.2059661 3.382747 0.0011515 0.2521644 ENSG00000259363
ENSG00000261520 1.3416498 0.5496398 3.381676 0.0011554 0.2521644 DLGAP1-AS5
ENSG00000175548 -0.5063777 4.4022251 -3.376397 0.0011747 0.2521644 ALG10B
ENSG00000185760 1.5278096 -0.4446505 3.375886 0.0011766 0.2521644 KCNQ5
ENSG00000151834 2.3592184 -1.6572592 3.372175 0.0011904 0.2521644 GABRA2
ENSG00000188107 0.4359750 3.0692274 3.334455 0.0013396 0.2754604 EYS
ENSG00000048462 -1.2491868 -0.2793089 -3.333326 0.0013444 0.2754604 TNFRSF17
ENSG00000136842 -0.8606898 1.1975239 -3.332867 0.0013463 0.2754604 TMOD1
ENSG00000170876 -0.1548197 6.2213758 -3.308470 0.0014525 0.2879399 TMEM43
ENSG00000226869 1.9505848 -1.0381730 3.308194 0.0014537 0.2879399 LHFPL3-AS1
ENSG00000185149 -1.2408556 0.7281455 -3.307857 0.0014552 0.2879399 NPY2R
ENSG00000203504 0.6387076 -0.3051535 3.299804 0.0014921 0.2920152 ENSG00000203504
ENSG00000187667 -0.8113413 -0.1035667 -3.291976 0.0015287 0.2959669 WHAMMP3

Differential expression within each cell type

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Gene set tests

NPC - roast

NGenes PropDown PropUp Direction PValue FDR PValue.Mixed FDR.Mixed
c4.GNF2_CD48 20 0.2500000 0.0000000 Down 0.01 0.9826775 0.32 0.9920713
c5.GO_REGULATION_OF_KERATINOCYTE_PROLIFERATION 18 0.1111111 0.2222222 Up 0.01 0.9826775 0.15 0.9920713
decreased_susceptibility_to_type_I_hypersensitivity_reaction 10 0.2000000 0.0000000 Down 0.01 0.9826775 0.19 0.9920713
regulation of nitric-oxide synthase activity 28 0.1428571 0.0000000 Down 0.01 0.9826775 0.44 0.9920713
regulation of monooxygenase activity 32 0.1250000 0.0000000 Down 0.01 0.9826775 0.63 0.9920713
Ligand-gated_ion_channel_transport 12 0.0000000 0.5000000 Up 0.02 0.9826775 0.04 0.9920713
c5.GO_GABA_RECEPTOR_ACTIVITY 11 0.0000000 0.3636364 Up 0.02 0.9826775 0.05 0.9920713
c2.MOOTHA_GLYCOLYSIS 17 0.2941176 0.0000000 Down 0.02 0.9826775 0.11 0.9920713
decreased_circulating_tumor_necrosis_factor_level 25 0.2800000 0.0000000 Down 0.02 0.9826775 0.12 0.9920713
c4.GNF2_VAV1 23 0.2608696 0.0000000 Down 0.02 0.9826775 0.33 0.9920713
increased_interleukin-1_beta_secretion 16 0.2500000 0.0000000 Down 0.02 0.9826775 0.15 0.9920713
c2.LANDEMAINE_LUNG_METASTASIS 16 0.0000000 0.2500000 Up 0.02 0.9826775 0.39 0.9920713
c4.GNF2_PAK2 22 0.2272727 0.0000000 Down 0.02 0.9826775 0.17 0.9920713
metalloexopeptidase activity 27 0.2222222 0.0000000 Down 0.02 0.9826775 0.43 0.9920713
c4.GNF2_HLA-C 33 0.2121212 0.0000000 Down 0.02 0.9826775 0.33 0.9920713
c5.GO_TRANS_GOLGI_NETWORK_TRANSPORT_VESICLE 27 0.1851852 0.0740741 Down 0.02 0.9826775 0.20 0.9920713
c2.MAGRANGEAS_MULTIPLE_MYELOMA_IGG_VS_IGA_UP 18 0.1666667 0.0000000 Down 0.02 0.9826775 0.19 0.9920713
myosin II complex 13 0.1538462 0.0000000 Down 0.02 0.9826775 0.42 0.9920713
il8cxcr1_pathway 20 0.1500000 0.0000000 Down 0.02 0.9826775 0.41 0.9920713
regulation of interleukin-1 secretion 9 0.0000000 0.1111111 Up 0.02 0.9826775 0.36 0.9920713

NPC - romer

NGenes Up Down Mixed
c7.GSE29618_LAIV_VS_TIV_FLU_VACCINE_DAY7_MONOCYTE_DN 157 1.01 0.01 0.01
c7.GSE14413_UNSTIM_VS_IFNB_STIM_NIH3T3_CELLS_UP 117 1.01 0.01 0.01
increased_susceptibility_to_bacterial_infection 100 1.01 0.01 0.01
c5.GO_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE 62 1.01 0.01 0.01
c5.GO_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS 47 1.01 0.01 0.01
negative regulation of inflammatory response 47 1.01 0.01 0.01
response to type I interferon 42 1.01 0.01 0.01
c5.GO_RECEPTOR_INTERNALIZATION 34 1.01 0.01 0.01
abnormal_cellular_extravasation 21 1.01 0.01 0.01
leukocyte cell-cell adhesion 18 1.01 0.01 0.01
c2.REACTOME_LIGAND_GATED_ION_CHANNEL_TRANSPORT 12 0.01 1.01 0.01
Ligand-gated_ion_channel_transport 12 0.01 1.01 0.01
c5.GO_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION 9 1.01 0.01 0.01
abnormal_response_to_infection 237 1.00 0.02 0.01
c5.GO_RESPONSE_TO_VIRUS 172 1.00 0.02 0.01
c7.GSE24574_BCL6_HIGH_TFH_VS_TCONV_CD4_TCELL_UP 160 1.00 0.02 0.01
c7.GSE22432_MULTIPOTENT_PROGENITOR_VS_CDC_UP 154 1.00 0.02 0.01
c7.GSE7460_FOXP3_MUT_VS_HET_ACT_TCONV_UP 136 1.00 0.02 0.01
c5.GO_DEFENSE_RESPONSE_TO_VIRUS 109 1.00 0.02 0.01
defense response to virus 96 1.00 0.02 0.01

Neuron - roast

NGenes PropDown PropUp Direction PValue FDR PValue.Mixed FDR.Mixed
c5.GO_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE 17 0.0000000 0.6470588 Up 0.01 0.5291039 0.01 0.7071165
c2.ONO_FOXP3_TARGETS_UP 15 0.4666667 0.0000000 Down 0.01 0.5291039 0.10 0.7071165
c2.NIKOLSKY_BREAST_CANCER_5P15_AMPLICON 20 0.4000000 0.0000000 Down 0.01 0.5291039 0.04 0.7071165
c5.GO_REGULATION_OF_INTERLEUKIN_17_PRODUCTION 8 0.3750000 0.0000000 Down 0.01 0.5291039 0.03 0.7071165
positive regulation of interferon-beta production 20 0.3500000 0.0000000 Down 0.01 0.5291039 0.14 0.7071165
gws3k-8.6_Red_vs_non-red_hair_color 15 0.3333333 0.0000000 Down 0.01 0.5291039 0.02 0.7071165
gws3k-8.6_Skin_sensitivity_to_sun 15 0.3333333 0.0000000 Down 0.01 0.5291039 0.05 0.7071165
abnormal_apical_ectodermal_ridge_morphology 16 0.0625000 0.3125000 Up 0.01 0.5291039 0.15 0.7071165
BIOCARTA_TOLL_PATHWAY 29 0.3103448 0.0689655 Down 0.01 0.5291039 0.08 0.7071165
regulation of interferon-beta production 26 0.3076923 0.0000000 Down 0.01 0.5291039 0.06 0.7071165
cone_pathway 13 0.0000000 0.3076923 Up 0.01 0.5291039 0.08 0.7071165
c2.PID_CONE_PATHWAY 13 0.0000000 0.3076923 Up 0.01 0.5291039 0.12 0.7071165
gws3k-8.6_Serum_albumin_level 17 0.2941176 0.0000000 Down 0.01 0.5291039 0.18 0.7071165
c5.GO_COP9_SIGNALOSOME 28 0.2857143 0.0000000 Down 0.01 0.5291039 0.04 0.7071165
receptor internalization 28 0.2857143 0.0357143 Down 0.01 0.5291039 0.09 0.7071165
c5.GO_BICELLULAR_TIGHT_JUNCTION_ASSEMBLY 28 0.2857143 0.0000000 Down 0.01 0.5291039 0.14 0.7071165
positive regulation of interleukin-6 production 21 0.2857143 0.0000000 Down 0.01 0.5291039 0.05 0.7071165
abnormal_pterygoid_process_morphology 14 0.0714286 0.2857143 Up 0.01 0.5291039 0.03 0.7071165
c5.GO_NECROPTOTIC_PROCESS 14 0.2857143 0.0000000 Down 0.01 0.5291039 0.10 0.7071165
actin-myosin filament sliding 18 0.2777778 0.0555556 Down 0.01 0.5291039 0.03 0.7071165

Neuron - romer

NGenes Up Down Mixed
c7.GSE5589_UNSTIM_VS_45MIN_LPS_AND_IL10_STIM_MACROPHAGE_UP 172 1.01 0.01 0.01
c7.GSE8384_CTRL_VS_B_ABORTUS_4H_MAC_CELL_LINE_DN 162 1.01 0.01 0.01
c7.GSE17721_CTRL_VS_GARDIQUIMOD_0.5H_BMDC_DN 159 1.01 0.01 0.01
c7.GSE1925_CTRL_VS_IFNG_PRIMED_MACROPHAGE_24H_IFNG_STIM_UP 158 1.01 0.01 0.01
c7.GSE21546_WT_VS_ELK1_KO_DP_THYMOCYTES_DN 151 1.01 0.01 0.01
c7.GSE3039_CD4_TCELL_VS_B1_BCELL_DN 146 1.01 0.01 0.01
protein complex scaffold 49 1.01 0.01 0.01
c5.GO_CELLULAR_CARBOHYDRATE_BIOSYNTHETIC_PROCESS 44 1.01 0.01 0.01
abnormal_temporal_bone_morphology 30 0.01 1.01 0.01
sensory perception of taste 26 0.01 1.01 0.01
c2.MAGRANGEAS_MULTIPLE_MYELOMA_IGG_VS_IGA_UP 18 1.01 0.01 0.01
abnormal_pterygoid_process_morphology 14 0.01 1.01 0.01
c5.GO_BITTER_TASTE_RECEPTOR_ACTIVITY 13 0.01 1.01 0.01
c7.GSE36527_CD69_NEG_VS_POS_TREG_CD62L_LOS_KLRG1_NEG_DN 177 1.00 0.02 0.01
c7.GSE45365_WT_VS_IFNAR_KO_CD8A_DC_MCMV_INFECTION_UP 177 1.00 0.02 0.01
negative regulation of cytokine production 89 1.00 0.02 0.01
c2.KYNG_RESPONSE_TO_H2O2_VIA_ERCC6_UP 37 1.00 0.02 0.01
abnormal_chorion_morphology 33 1.00 0.02 0.01
c5.GO_POSITIVE_REGULATION_OF_INTERFERON_GAMMA_PRODUCTION 27 1.00 0.02 0.01
c7.GSE3982_CTRL_VS_LPS_1H_NEUTROPHIL_DN 159 0.99 0.03 0.01

Compare logFC between celltypes

Genes with FDR < 30% within NPC or neuron separately

Neuron

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -4.1176470 -2.0458924 -6.121625 0.00e+00 0.0008056 ENSG00000230847
ENSG00000173894 0.5551547 5.3493957 4.617878 1.63e-05 0.1543658 CBX2
ENSG00000115828 -1.7332719 0.6431161 -4.505460 2.47e-05 0.1560023 QPCT
ENSG00000164669 -1.2307287 -0.2461149 -4.337493 4.56e-05 0.2158049 INTS4L1
ENSG00000164930 -0.7391163 4.8643554 -4.248241 6.29e-05 0.2378761 FZD6

NPC

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -3.5818061 -2.0458924 -5.077991 2.80e-06 0.0536223 ENSG00000230847
ENSG00000226259 -1.2943834 2.3980778 -4.621129 1.61e-05 0.1046486 GTF2H2B
ENSG00000164930 -0.8172728 4.8643554 -4.613377 1.66e-05 0.1046486 FZD6
ENSG00000162618 -2.3869758 -0.7365519 -4.429296 3.27e-05 0.1546567 ELTD1
ENSG00000236725 -1.1055833 0.4658067 -4.236436 6.56e-05 0.2481135 ENSG00000236725

Effect of correcting for Fibroblast score on case-control t-statistics in NPCs

We have demonstrated that correcting for the fibroblast score is important, especially in boosting concordance with HBCC. So what genes are affected by this correction? In order to test this, I compared the absolute value of the t-statstic (the test-statistic used compute the p-value) from the adjusted and unadjusted test.

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.REACTOME_RNA_POL_I_PROMOTER_OPENING 53 3.11 22 7.07 5.205652e-14
c2.REACTOME_AMYLOIDS 61 3.58 23 6.42 1.630978e-13
KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 79 4.64 26 5.60 1.805959e-13
c2.KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 80 4.70 26 5.53 2.528446e-13
kegg_Systemic_lupus_erythematosus 80 4.70 26 5.53 2.528446e-13
c5.GO_DNA_PACKAGING_COMPLEX 80 4.70 25 5.32 1.977977e-12
c2.REACTOME_PACKAGING_OF_TELOMERE_ENDS 41 2.41 18 7.48 3.281350e-12
KEGG_ALCOHOLISM 149 8.75 34 3.89 5.041777e-12
kegg_Alcoholism 149 8.75 34 3.89 5.041777e-12
CMC-modules_forestgreen 28 1.64 15 9.12 5.556191e-12
c2.REACTOME_RNA_POL_I_TRANSCRIPTION 78 4.58 24 5.24 7.968194e-12
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 9.69 35 3.61 2.248728e-11
c2.REACTOME_MEIOTIC_RECOMBINATION 71 4.17 22 5.28 5.078763e-11
c2.REACTOME_MEIOSIS 95 5.58 24 4.30 7.564072e-10
c2.REACTOME_TELOMERE_MAINTENANCE 67 3.93 20 5.08 8.074538e-10

up only

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
secondary_FMRP-targets 770 22.64 55 2.43 8.964789e-10
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 15.20 42 2.76 2.518142e-09
CMC-modules_red 689 20.25 48 2.37 2.541420e-08
c5.GO_CELL_PROJECTION 1508 44.33 80 1.80 1.172295e-07
c5.GO_CELL_PROJECTION_PART 809 23.78 51 2.14 2.186483e-07
c5.GO_SYNAPSE 677 19.90 45 2.26 2.751798e-07
kirov_psych.ed.set_mGluR5 37 1.09 9 8.27 9.066695e-07
kirov_synaptic.sets_mGluR5 37 1.09 9 8.27 9.066695e-07
primary_mGluR5 37 1.09 9 8.27 9.066695e-07
c2.WANG_LSD1_TARGETS_DN 31 0.91 8 8.78 2.282486e-06
primary_PSD_(human_core) 644 18.93 41 2.17 2.852382e-06
c5.GO_CYTOSKELETAL_PROTEIN_BINDING 693 20.37 43 2.11 3.130646e-06
cav2_Cav2::ALL 193 5.67 19 3.35 4.282863e-06
c2.BLALOCK_ALZHEIMERS_DISEASE_DN 1184 34.81 62 1.78 5.870449e-06
c4.MODULE_100 467 13.73 32 2.33 8.398773e-06

downonly

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.REACTOME_RNA_POL_I_PROMOTER_OPENING 53 1.55 22 14.15 2.321068e-20
c2.REACTOME_AMYLOIDS 61 1.79 23 12.85 4.358139e-20
KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 79 2.32 25 10.79 1.461924e-19
c2.KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 80 2.35 25 10.65 2.069585e-19
c5.GO_DNA_PACKAGING_COMPLEX 80 2.35 25 10.65 2.069585e-19
kegg_Systemic_lupus_erythematosus 80 2.35 25 10.65 2.069585e-19
c2.REACTOME_RNA_POL_I_TRANSCRIPTION 78 2.29 23 10.05 2.526080e-17
c2.REACTOME_MEIOTIC_RECOMBINATION 71 2.08 22 10.56 3.831306e-17
CMC-modules_forestgreen 28 0.82 15 18.26 2.155808e-16
KEGG_ALCOHOLISM 149 4.37 29 6.64 3.733569e-16
kegg_Alcoholism 149 4.37 29 6.64 3.733569e-16
c5.GO_PROTEIN_DNA_COMPLEX 141 4.14 27 6.53 6.093019e-15
c5.GO_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC 89 2.61 22 8.43 7.612436e-15
c2.REACTOME_PACKAGING_OF_TELOMERE_ENDS 41 1.20 16 13.30 1.218042e-14
c5.GO_CHROMATIN_SILENCING 73 2.14 20 9.34 1.509248e-14

Effect of correcting for Fibroblast score on case-control t-statistics in Neurons

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
tissue_exp_brain 495 29.13 85 2.92 1.703722e-19
CMC-modules_red 689 40.55 89 2.19 1.306218e-12
c5.GO_SYNAPSE_PART 549 32.31 74 2.29 1.522632e-11
c5.GO_SYNAPSE 677 39.85 85 2.13 1.977615e-11
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION 177 10.42 36 3.46 4.439413e-11
c5.GO_NEURON_PART 1088 64.04 117 1.83 7.934100e-11
c4.MODULE_47 196 11.54 37 3.21 2.288108e-10
secondary_FMRP-targets 770 45.32 90 1.99 2.311185e-10
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 9.71 33 3.40 4.544049e-10
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 20.42 51 2.50 1.252737e-09
c5.GO_PRESYNAPTIC_PROCESS_INVOLVED_IN_SYNAPTIC_TRANSMISSION 101 5.94 24 4.04 3.009981e-09
c2.MEISSNER_NPC_HCP_WITH_H3K4ME2 390 22.95 54 2.35 3.612506e-09
c5.GO_NEURON_PROJECTION 835 49.15 91 1.85 6.490311e-09
abnormal_motor_coordination_balance 458 26.96 59 2.19 1.054544e-08
c5.GO_NEUROTRANSMITTER_TRANSPORT 133 7.83 27 3.45 1.239876e-08

up only

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 15.10 46 3.05 1.583029e-11
CMC-modules_red 689 20.12 54 2.68 3.329240e-11
tissue_exp_brain 495 14.46 43 2.97 1.630936e-10
secondary_FMRP-targets 770 22.49 52 2.31 1.434069e-08
c2.BLALOCK_ALZHEIMERS_DISEASE_DN 1184 34.58 68 1.97 5.070287e-08
c5.GO_SYNAPSE 677 19.77 46 2.33 8.738854e-08
c5.GO_PRESYNAPTIC_PROCESS_INVOLVED_IN_SYNAPTIC_TRANSMISSION 101 2.95 15 5.09 2.271475e-07
c5.GO_SYNAPSE_PART 549 16.03 39 2.43 2.879986e-07
c4.MODULE_100 467 13.64 35 2.57 3.434816e-07
primary_PSD_(human_core) 644 18.81 43 2.29 3.811836e-07
c4.MODULE_66 474 13.84 35 2.53 4.881700e-07
kirov_psych.ed.set_mGluR5 37 1.08 9 8.33 8.584918e-07
kirov_synaptic.sets_mGluR5 37 1.08 9 8.33 8.584918e-07
primary_mGluR5 37 1.08 9 8.33 8.584918e-07
c2.REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES 159 4.64 18 3.88 9.357542e-07

downonly

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 4.89 23 4.70 6.649058e-10
tissue_exp_brain 495 14.68 42 2.86 8.851474e-10
c2.WONG_ADULT_TISSUE_STEM_MODULE 591 17.52 46 2.62 2.189234e-09
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION 177 5.25 22 4.19 1.376309e-08
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 10.29 31 3.01 4.817120e-08
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223 6.61 24 3.63 5.156047e-08
c2.CUI_TCF21_TARGETS_2_DN 744 22.06 50 2.27 5.305225e-08
c5.GO_NEURON_PART 1088 32.26 64 1.98 9.817372e-08
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 36.32 69 1.90 1.538746e-07
c5.GO_LEUKOCYTE_MEDIATED_IMMUNITY 94 2.79 14 5.02 6.656525e-07
c5.GO_LYMPHOCYTE_MEDIATED_IMMUNITY 69 2.05 12 5.86 7.622998e-07
c5.GO_CELL_PART_MORPHOGENESIS 556 16.49 38 2.30 1.544832e-06
c5.GO_B_CELL_MEDIATED_IMMUNITY 40 1.19 9 7.59 1.979220e-06
c5.GO_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS 867 25.71 51 1.98 2.241517e-06
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 397 11.77 30 2.55 2.781861e-06

Effective sample size calculations

## Using ID, CellType as id variables

Check Fibroblast signature, NPC and Neurons for CD73 (NT5E) and CD271 (NGFR)

SessionInfo

## R version 3.4.1 (2017-06-30)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 14.04.5 LTS
## 
## Matrix products: default
## BLAS/LAPACK: /opt/intel/compilers_and_libraries_2017.4.196/linux/mkl/lib/intel64_lin/libmkl_gf_lp64.so
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## attached base packages:
##  [1] grid      compiler  stats4    parallel  stats     graphics  grDevices
##  [8] datasets  utils     methods   base     
## 
## other attached packages:
##  [1] sets_1.0-17                VennDiagram_1.6.17        
##  [3] futile.logger_1.4.3        pheatmap_1.0.8            
##  [5] GSEABase_1.38.2            graph_1.54.0              
##  [7] annotate_1.54.0            XML_3.98-1.9              
##  [9] AnnotationDbi_1.38.2       HTSanalyzeR_2.28.0        
## [11] igraph_1.1.2               gage_2.26.1               
## [13] GGally_1.3.2               knitr_1.17                
## [15] qvalue_2.8.0               reshape2_1.4.2            
## [17] xtable_1.8-2               colortools_0.1.5          
## [19] preprocessCore_1.38.1      DESeq2_1.16.1             
## [21] SummarizedExperiment_1.6.5 DelayedArray_0.2.7        
## [23] matrixStats_0.52.2         GenomicRanges_1.28.5      
## [25] GenomeInfoDb_1.12.2        IRanges_2.10.3            
## [27] S4Vectors_0.14.5           readr_1.1.1               
## [29] latex2exp_0.4.0            mixtools_1.1.0            
## [31] ape_4.1                    ggrepel_0.7.0             
## [33] variancePartition_1.6.0    Biobase_2.36.2            
## [35] BiocGenerics_0.22.0        ggplot2_2.2.1             
## [37] gridExtra_2.3              edgeR_3.18.1              
## [39] limma_3.32.7               synapseClient_1.15-0      
## [41] doParallel_1.0.11          iterators_1.0.8           
## [43] foreach_1.4.3             
## 
## loaded via a namespace (and not attached):
##   [1] backports_1.1.1         Hmisc_4.0-3            
##   [3] splots_1.42.0           plyr_1.8.4             
##   [5] lazyeval_0.2.0          splines_3.4.1          
##   [7] gmp_0.5-13.1            BiocParallel_1.10.1    
##   [9] digest_0.6.12           BiocInstaller_1.26.1   
##  [11] htmltools_0.3.6         gdata_2.18.0           
##  [13] magrittr_1.5            checkmate_1.8.4        
##  [15] memoise_1.1.0           cluster_2.0.6          
##  [17] prada_1.52.0            Biostrings_2.44.2      
##  [19] colorspace_1.3-2        blob_1.1.0             
##  [21] rrcov_1.4-3             RCurl_1.95-4.8         
##  [23] genefilter_1.58.1       lme4_1.1-14            
##  [25] survival_2.41-3         gtable_0.2.0           
##  [27] zlibbioc_1.22.0         XVector_0.16.0         
##  [29] RankProd_3.2.0          Rmpfr_0.6-1            
##  [31] cellHTS2_2.40.0         DEoptimR_1.0-8         
##  [33] scales_0.5.0            futile.options_1.0.0   
##  [35] vsn_3.44.0              mvtnorm_1.0-6          
##  [37] DBI_0.7                 Rcpp_0.12.13           
##  [39] htmlTable_1.9           foreign_0.8-69         
##  [41] bit_1.1-12              Formula_1.2-2          
##  [43] htmlwidgets_0.9         httr_1.3.1             
##  [45] gplots_3.0.1            RColorBrewer_1.1-2     
##  [47] acepack_1.4.1           pkgconfig_2.0.1        
##  [49] reshape_0.8.7           nnet_7.3-12            
##  [51] locfit_1.5-9.1          labeling_0.3           
##  [53] rlang_0.1.2             munsell_0.4.3          
##  [55] tools_3.4.1             RSQLite_2.0            
##  [57] evaluate_0.10.1         stringr_1.2.0          
##  [59] yaml_2.1.14             bit64_0.9-7            
##  [61] robustbase_0.92-7       caTools_1.17.1         
##  [63] KEGGREST_1.16.1         RBGL_1.52.0            
##  [65] nlme_3.1-131            BioNet_1.36.0          
##  [67] biomaRt_2.32.1          pbkrtest_0.4-7         
##  [69] png_0.1-7               affyio_1.46.0          
##  [71] statmod_1.4.30          tibble_1.3.4           
##  [73] geneplotter_1.54.0      pcaPP_1.9-72           
##  [75] stringi_1.1.5           highr_0.6              
##  [77] lattice_0.20-35         Matrix_1.2-11          
##  [79] nloptr_1.0.4            data.table_1.10.4      
##  [81] bitops_1.0-6            colorRamps_2.3         
##  [83] R6_2.2.2                latticeExtra_0.6-28    
##  [85] affy_1.54.0             hwriter_1.3.2          
##  [87] KernSmooth_2.23-15      codetools_0.2-15       
##  [89] lambda.r_1.2            MASS_7.3-47            
##  [91] gtools_3.5.0            Category_2.42.1        
##  [93] rprojroot_1.2           rjson_0.2.15           
##  [95] GenomeInfoDbData_0.99.0 hms_0.3                
##  [97] rpart_4.1-11            minqa_1.2.4            
##  [99] rmarkdown_1.6           segmented_0.5-2.2      
## [101] base64enc_0.1-3